tbuckley/cabot-search huggingface dataset:
Aligning Value-Based Payments With Health Equity
Authors: Amol S. Navathe, Joshua M. Liao
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer
Authors: Walid K. Chatila, Jin K. Kim, Henry Walch, Michael R. Marco, Chin-Tung Chen, Fan Wu, Dana M. Omer, Danny N. Khalil, Karuna Ganesh, Xuan Qu, Anisha Luthra, Seo-Hyun Choi, Yu-Jui Ho, Ritika Kundra, Katharine I. Groves, Oliver S. Chow, Andrea Cercek, Martin R. Weiser, Maria Widmar, Iris H. Wei, Emmanouil P. Pappou, Garrett M. Nash, Philip B. Paty, Qian Shi, Efsevia Vakiani, S. Duygu Selcuklu, Mark T. A. Donoghue, David B. Solit, Michael F. Berger, Jinru Shia, Raphael Pelossof, Paul B. Romesser, Rona Yaeger, J. Joshua Smith, Nikolaus Schultz, Francisco Sanchez-Vega, Julio Garcia-Aguilar
Journal: Nature Medicine (2022)
Itaconate for lupus remission: the next therapeutic frontier? Comment on the article by Blanco et al
Authors: Qi Huang, Wang‐Dong Xu
Journal: Arthritis & Rheumatology (2022)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Identification and Characterization of Early and Late Prescribes in General Practice
Authors: B Strickland-Hodge, M H Jepson
Journal: Journal of the Royal Society of Medicine (1982)

National Health Service prescriptions written by general medical practitioners in one urban Area were analysed over a fifteen-month period to classify doctors into those who prescribed a named drug early or relatively later in its market life. A questionnaire, designed to answer a number of hypotheses intended to characterize these groups of practitioners, was mailed to the 100 doctors in each group. Statistical analysis of the results suggests that there are several identifiable characteristic differences between ‘early’ and ‘late’ prescribers. Early prescribers have larger list sizes than late prescribers and rely more on industrial sources for information about drugs.
Use of Drugs by the Elderly
Authors: Patrick J Kiernan, Jeffrey B Isaacs
Journal: Journal of the Royal Society of Medicine (1981)

This paper outlines the use of both prescribed and non-prescribed medication by the elderly in the community. The study examined a number of factors related to medication including compliance, the types of drugs taken, the manner in which drugs were stored and disposed of, and the advice that patients received. The findings revealed a lack of coordination of responsibility in the management of patients’ medicines leading to inappropriate drug use, posing a potential risk to the patient. It is against this background that we propose that the role of the general practice pharmacist should be extended within a structured health care programme; pharmacists should be encouraged to keep total medication records on patients of 65 and over.
Progression and survival of MBL: a screening study of 10 139 individuals
Authors: Susan L. Slager, Sameer A. Parikh, Sara J. Achenbach, Aaron D. Norman, Kari G. Rabe, Nicholas J. Boddicker, Janet E. Olson, Geffen Kleinstern, Connie E. Lesnick, Timothy G. Call, James R. Cerhan, Celine M. Vachon, Neil E. Kay, Esteban Braggio, Curtis A. Hanson, Tait D. Shanafelt
Journal: Blood (2022)

Monoclonal B-cell lymphocytosis (MBL) is a common hematological premalignant condition that is understudied in screening cohorts. MBL can be classified into low-count (LC) and high-count (HC) types based on the size of the B-cell clone. Using the Mayo Clinic Biobank, we screened for MBL and evaluated its association with future hematologic malignancy and overall survival (OS). We had a two-stage study design including discovery and validation cohorts. We screened for MBL using an eight-color flow-cytometry assay. Medical records were abstracted for hematological cancers and death. We used Cox regression to evaluate associations and estimate hazard ratios and 95% confidence intervals (CIs), adjusting for age and sex. We identified 1712 (17%) individuals with MBL (95% LC-MBL), and the median follow-up time for OS was 34.4 months with 621 individuals who died. We did not observe an association with OS among individuals with LC-MBL (P = .78) but did among HC-MBL (hazard ratio, 1.8; 95% CI, 1.1-3.1; P = .03). Among the discovery cohort with a median of 10.0 years follow-up, 31 individuals developed hematological cancers with two-thirds being lymphoid malignancies. MBL was associated with 3.6-fold risk of hematological cancer compared to controls (95% CI, 1.7-7.7; P < .001) and 7.7-fold increased risk for lymphoid malignancies (95% CI:3.1-19.2; P < .001). LC-MBL was associated with 4.3-fold risk of lymphoid malignancies (95% CI, 1.4-12.7; P = .009); HC-MBL had a 74-fold increased risk (95% CI, 22-246; P < .001). In this large screening cohort, we observed similar survival among individuals with and without LC-MBL, yet individuals with LC-MBL have a fourfold increased risk of lymphoid malignancies. Accumulating evidence indicates that there are clinical consequences to LC-MBL, a condition that affects 8 to 10 million adults in the United States.
Apolipoprotein E ϵ4 and Incidence of Alzheimer Disease in a Community Population of Older Persons
Authors: Denis A. Evans
Journal: JAMA (1997)

<h3>Objective.</h3> —To examine the relation between apolipoprotein E status and risk of Alzheimer disease (AD) in a defined population and estimate the fraction of incident AD attributable to the ϵ4 allele. <h3>Design.</h3> —Community-based cohort study. <h3>Setting.</h3> —East Boston, Mass. <h3>Participants.</h3> —A random sample of 578 community residents aged 65 years and older free of AD. <h3>Main Outcome Measure.</h3> —Clinical diagnosis of AD by uniform, structured evaluation. <h3>Results.</h3> —The increased risk of AD associated with the presence of the ϵ4 allele was less than that found in most family and case-control studies. Persons with the ϵ4/ϵ4 or ϵ3/ϵ4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the ϵ3/ϵ3 genotype. The ϵ4 allele accounted for a fairly small fraction of the incidence of AD; if the allele did not exist or had no effect on disease risk, the incidence would be reduced by only 13.7%. The effect of the ϵ4 allele on risk of AD did not appear to vary with age. <h3>Conclusions.</h3> —The apolipoprotein E ϵ4 allele is an important genetic risk factor for AD but accounts for a fairly small fraction of disease occurrence in this population-based study. Continued efforts to identify other environmental and genetic risk factors are warranted.
Integrating basic science with translational research: the 13th International Podocyte Conference 2021
Authors: Franziska Lausecker, Sybille Koehler, Maryline Fresquet, Richard W. Naylor, Pinyuan Tian, Nicola Wanner, Fabian Braun, Linus Butt, Tobias B. Huber, Rachel Lennon
Journal: Kidney International (2022)

The 13th International Podocyte Conference was held in Manchester, UK, and online from July 28 to 30, 2021. Originally planned for 2020, this biannual meeting was postponed by a year because of the coronavirus disease 2019 (COVID-19) pandemic and proceeded as an innovative hybrid meeting. In addition to in-person attendance, online registration was offered, and this attracted 490 conference registrations in total. As a Podocyte Conference first, a day for early-career researchers was introduced. This premeeting included talks from graduate students and postdoctoral researchers. It gave early career researchers the opportunity to ask a panel, comprising academic leaders and journal editors, about career pathways and the future for podocyte research. The main meeting over 3 days included a keynote talk and 4 focused sessions each day incorporating invited talks, followed by selected abstract presentations, and an open panel discussion. The conference concluded with a Patient Day, which brought together patients, clinicians, researchers, and industry representatives. The Patient Day was an interactive and diverse day. As well as updates on improving diagnosis and potential new therapies, the Patient Day included a PodoArt competition, exercise and cooking classes with practical nutrition advice, and inspirational stories from patients and family members. This review summarizes the exciting science presented during the 13th International Podocyte Conference and demonstrates the resilience of researchers during a global pandemic.
Resolving conflict about treatment for seriously ill children
Authors: Dominic JC Wilkinson
Journal: BMJ (2022)

On Saturday 6 August, another high profile case of conflict between parents and doctors about the treatment for a seriously ill child came to an end after treatment was withdrawn from 12 year old Archie Battersbee.Archie is the latest in a series of such cases in the UK to reach public attention in the past five years.Media attention given to cases like this can give the impression that conflict about treatment for critically ill children is common, and that the UK is unusual in having so many disputes.But although it is difficult to be sure (there are little or no comparative data), both of these impressions are likely incorrect.Futility disputes are well described and occur regularly, albeit infrequently, in many other countries. 1 The majority of cases of disagreement are not reported because they do not end up going to court.However, reflecting on the outcome of less high profile cases is important, since it may point to ways of resolving disagreement.Conceptually, there are five different possible ways that conflict may end.
Phenotypically-defined stages of leukemia arrest predict main driver mutations subgroups, and outcome in acute myeloid leukemia
Authors: François Vergez, Laetitia Largeaud, Sarah Bertoli, Marie-Laure Nicolau, Jean-Baptiste Rieu, Inès Vergnolle, Estelle Saland, Audrey Sarry, Suzanne Tavitian, Françoise Huguet, Muriel Picard, Jean-Philippe Vial, Nicolas Lechevalier, Audrey Bidet, Pierre-Yves Dumas, Arnaud Pigneux, Isabelle Luquet, Véronique Mansat-De Mas, Eric Delabesse, Martin Carroll, Gwenn Danet-Desnoyers, Jean-Emmanuel Sarry, Christian Récher
Journal: Blood Cancer Journal (2022)

Abstract Classifications of acute myeloid leukemia (AML) patients rely on morphologic, cytogenetic, and molecular features. Here we have established a novel flow cytometry-based immunophenotypic stratification showing that AML blasts are blocked at specific stages of differentiation where features of normal myelopoiesis are preserved. Six stages of leukemia differentiation-arrest categories based on CD34, CD117, CD13, CD33, MPO, and HLA-DR expression were identified in two independent cohorts of 2087 and 1209 AML patients. Hematopoietic stem cell/multipotent progenitor-like AMLs display low proliferation rate, inv(3) or RUNX1 mutations, and high leukemic stem cell frequency as well as poor outcome, whereas granulocyte–monocyte progenitor-like AMLs have CEBPA mutations, RUNX1-RUNX1T1 or CBFB-MYH11 translocations, lower leukemic stem cell frequency, higher chemosensitivity, and better outcome. NPM1 mutations correlate with most mature stages of leukemia arrest together with TET2 or IDH mutations in granulocyte progenitors-like AML or with DNMT3A mutations in monocyte progenitors-like AML. Overall, we demonstrate that AML is arrested at specific stages of myeloid differentiation (SLA classification) that significantly correlate with AML genetic lesions, clinical presentation, stem cell properties, chemosensitivity, response to therapy, and outcome.
Author Correction: A novel AI device for real-time optical characterization of colorectal polyps
Authors: Carlo Biffi, Pietro Salvagnini, Nhan Ngo Dinh, Cesare Hassan, Prateek Sharma, Giulio Antonelli, Halim Awadie, Sebastian Bernhofer, Sabela Carballal, Mário Dinis-Ribeiro, Agnès Fernández-Clotet, Glòria Fernández Esparrach, Ian Gralnek, Yuta Higasa, Taku Hirabayashi, Tatsuki Hirai, Mineo Iwatate, Miki Kawano, Markus Mader, Andreas Maieron, Sebastian Mattes, Tastuya Nakai, Ingrid Ordas, Raquel Ortigão, Oswaldo Ortiz Zúñiga, Maria Pellisé, Cláudia Pinto, Florian Riedl, Ariadna Sánchez, Emanuel Steiner, Yukari Tanaka, Andrea Cherubini
Journal: npj Digital Medicine (2022)
γ-secretase inhibitors augment efficacy of BCMA-targeting bispecific antibodies against multiple myeloma cells without impairing T-cell activation and differentiation
Authors: Hailin Chen, Tengteng Yu, Liang Lin, Lijie Xing, Shih-Feng Cho, Kenneth Wen, Kimberly Aardalen, Adwait Oka, Joni Lam, Mike Daley, Haihui Lu, Nikhil Munshi, Kenneth C. Anderson, Yu-Tzu Tai
Journal: Blood Cancer Journal (2022)

Abstract We here defined the impacts of γ-secretase inhibitors (GSIs) on T-cell-dependent BCMA-specific multiple myeloma (MM) cell lysis and immunomodulatory effects induced by bispecific antibodies (BisAbs). GSIs-induced membrane BCMA (mBCMA) accumulation reached near maximum within 4 h and sustained over 42h-study period on MM cell lines and patient MM cells. GSIs, i.e., 2 nM LY-411575 or 1 μM DAPT, robustly increased mBCMA densities on CD138 + but not CD3 + patient cells, concomitantly with minimum soluble/shed BCMA (sBCMA) in 1 day-culture supernatants. In ex vivo MM-T-cell co-cultures, GSIs overcame sBCMA-inhibited MM cell lysis and further enhanced autologous patient MM cell lysis induced by BCMAxCD3 BisAbs, accompanied by significantly enhanced cytolytic markers (CD107a, IFNγ, IL2, and TNFα) in patient T cells. In longer 7 day-co-cultures, LY-411575 minimally affected BCMAxCD3 BisAb (PL33)-induced transient expression of checkpoint (PD1, TIGIT, TIM3, LAG3) and co-stimulatory (41BB, CD28) proteins, as well as time-dependent increases in % effector memory/central memory subsets and CD8/CD4 ratios in patient T cells. Importantly, LY41157 rapidly cleared sBCMA from circulation of MM-bearing NSG mice reconstituted with human T cells and significantly enhanced anti-MM efficacy of PL33 with prolonged host survival. Taken together, these results further support ongoing combination BCMA-targeting immunotherapies with GSI clinical studies to improve patient outcome.
Single-cell genomic and transcriptomic landscapes of primary and metastatic colorectal cancer tumors
Authors: Rui Wang, Jingyun Li, Xin Zhou, Yunuo Mao, Wendong Wang, Shuai Gao, Wei Wang, Yuan Gao, Kexuan Chen, Shuntai Yu, Xinglong Wu, Lu Wen, Hao Ge, Wei Fu, Fuchou Tang
Journal: Genome Medicine (2022)

Abstract Background Colorectal cancer (CRC) ranks as the second-leading cause of cancer-related death worldwide with metastases being the main cause of cancer-related death. Here, we investigated the genomic and transcriptomic alterations in matching adjacent normal tissues, primary tumors, and metastatic tumors of CRC patients. Methods We performed whole genome sequencing (WGS), multi-region whole exome sequencing (WES), simultaneous single-cell RNA-Seq, and single-cell targeted cDNA Sanger sequencing on matching adjacent normal tissues, primary tumors, and metastatic tumors from 12 metastatic colorectal cancer patients ( n =84 for genomes, n =81 for exomes, n =9120 for single cells). Patient-derived tumor organoids were used to estimate the anti-tumor effects of a PPAR inhibitor, and self-renewal and differentiation ability of stem cell-like tumor cells. Results We found that the PPAR signaling pathway was prevalently and aberrantly activated in CRC tumors. Blocking of PPAR pathway both suppressed the growth and promoted the apoptosis of CRC organoids in vitro, indicating that aberrant activation of the PPAR signaling pathway plays a critical role in CRC tumorigenesis. Using matched samples from the same patient, distinct origins of the metastasized tumors between lymph node and liver were revealed, which was further verified by both copy number variation and mitochondrial mutation profiles at single-cell resolution. By combining single-cell RNA-Seq and single-cell point mutation identification by targeted cDNA Sanger sequencing, we revealed important phenotypic differences between cancer cells with and without critical point mutations ( KRAS and TP53 ) in the same patient in vivo at single-cell resolution. Conclusions Our data provides deep insights into how driver mutations interfere with the transcriptomic state of cancer cells in vivo at a single-cell resolution. Our findings offer novel knowledge on metastatic mechanisms as well as potential markers and therapeutic targets for CRC diagnosis and therapy. The high-precision single-cell RNA-seq dataset of matched adjacent normal tissues, primary tumors, and metastases from CRCs may serve as a rich resource for further studies.
Editor's Note: Diphenyl Difluoroketone: A Curcumin Derivative with Potent <i>In Vivo</i> Anticancer Activity
Authors: Dharmalingam Subramaniam, Randal May, Sripathi M. Sureban, Katherine B. Lee, Robert George, Periannan Kuppusamy, Rama P. Ramanujam, Kalman Hideg, Brian K. Dieckgraefe, Courtney W. Houchen, Shrikant Anant
Journal: Cancer Research (2022)

The editors are publishing this note to alert readers to concerns with this article (1).Specifically, in Fig. 2 the actin bands used in Fig. 2C are the same as the actin bands used as a loading control for Bcl-2 in Fig. 2D.In addition, in Fig. 2D, the actin loading control bands for Bcl-xL were vertically flipped and reused for the actin loading control bands for Bax.
Routine use of granulocyte colony-stimulating factor is not cost-effective and does not increase patient comfort in the treatment of small-cell lung cancer: an analysis using a Markov model.
Authors: C. Chouaid, L. Bassinet, C. Fuhrman, I. Monnet, B. Housset
Journal: Journal of Clinical Oncology (1998)

PURPOSE The clinical indications and economic consequences of human granulocyte colony-stimulating factor (G-CSF) prescription during small-cell lung cancer (SCLC) chemotherapy remain controversial. The aim of this study, based on a Markov model, was to assess the impact of routine G-CSF use in the treatment of SCLC on costs and patient comfort. Markov models allow the modeling SCLC chemotherapy, in which the risk of febrile neutropenia (FN) is continuous over time and may occur more than once. PATIENTS AND METHODS We used a Markov model to compare three strategies: a chemotherapy dose reduction after FN and nonuse of G-CSF ("never" strategy), secondary use of G-CSF ("CSF if FN" strategy) and primary use of G-CSF ("systematic CSF" strategy). Model baseline probabilities were based on a review of medical records for all patients (n = 39) treated for SCLC in our unit during 1993 (when G-CSF was not used) and on published reductions in the incidence of FN obtained by using G-CSF. Two different types of rewards were used: a cost-utility scale that took into account the costs of FN (CFN) episodes and G-CSF (CCSF) courses; and a comfort-utility scale that took into account the discomfort of FN and G-CSF therapy. Costs were analyzed from the health care payer's perspective and utilities were assessed prospectively in standardized interviews with treated SCLC patients. RESULTS The never strategy was the least costly ($4,875 [United States] versus $5,816 and $7,690 for CSF if FN and systematic CSF) and gave the highest comfort value (378 U v 365 and 327 for CSF if FN and systematic CSF). Sensitivity analyses showed that the never strategy remains the less costly when the probability of a first FN episode was less than 49%, the probability of FN recurrence was less than 60%, or the CFN was less than $6,077, or the CCSF was greater than $863. In terms of patient comfort, the never strategy was the best choice, except for patients who considered that a course of G-CSF caused little or no discomfort, whether or not it prevented FN. CONCLUSION Routine use of G-CSF during SCLC chemotherapy is not justified by clinical benefits, improved patient comfort, or economic considerations.
PerSVade: personalized structural variant detection in any species of interest
Authors: Miquel Àngel Schikora-Tamarit, Toni Gabaldón
Journal: Genome biology (2022)

Abstract Structural variants (SVs) underlie genomic variation but are often overlooked due to difficult detection from short reads. Most algorithms have been tested on humans, and it remains unclear how applicable they are in other organisms. To solve this, we develop perSVade (personalized structural variation detection), a sample-tailored pipeline that provides optimally called SVs and their inferred accuracy, as well as small and copy number variants. PerSVade increases SV calling accuracy on a benchmark of six eukaryotes. We find no universal set of optimal parameters, underscoring the need for sample-specific parameter optimization. PerSVade will facilitate SV detection and study across diverse organisms.
Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on Disability
Authors: Lonny Shavelson, Thaddeus M. Pope, Margaret Pabst Battin, Alicia Ouellette, Benzi Kluger
Journal: The American Journal of Bioethics (2022)

Terminally ill patients in 10 states plus Washington, D.C. have the right to take prescribed medications to end their lives (medical aid in dying). But otherwise-eligible patients with neuromuscular disabilities (ALS and other illnesses) are excluded if they are physically unable to "self-administer" the medications without assistance. This exclusion is incompatible with disability rights laws that mandate assistance to provide equal access to health care. This contradiction between aid-in-dying laws and disability rights laws can force patients and clinicians into violating one or the other, potentially creating an underclass of patients denied medical care that is available to those with other (less physically disabling) terminal illnesses. The immediacy of this issue is demonstrated by a lawsuit in Federal court filed in August 2021, requesting assistance in self-administration for terminally ill patients with neuromuscular diseases. This paper discusses the background of this conflict, the ethical issues at the heart of the dilemma, and recommends potential remedies.
Publisher Correction: Safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1/2a study
Authors: Marja K. Puurunen, Jerry Vockley, Shawn L. Searle, Stephanie J. Sacharow, John A. Phillips, William S. Denney, Benjamin D. Goodlett, David A. Wagner, Larry Blankstein, Mary J. Castillo, Mark R. Charbonneau, Vincent M. Isabella, Vasu V. Sethuraman, Richard J. Riese, Caroline B. Kurtz, Aoife M. Brennan
Journal: Nature Metabolism (2022)